Control of mouse hepatocyte proliferation and ploidy by p53 and p53ser246 mutation in vivo

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
L YinS Sell

Abstract

The effect of expression of the p53 gene, in the presence or absence of the p53ser246 mutation (p53*), on ploidization (image cytometry), proliferation (expression of proliferating cell nuclear antigen and radioactive thymidine histoautoradiography), and apoptosis (in situ detection of DNA fragments) is determined in hepatocytes of p53-null and p53*-transgenic mice. The mouse p53ser246 mutation is equivalent to the p53ser249 mutation found in human hepatomas associated with hepatitis B virus infection and aflatoxin exposure. The hepatocytes of heterozygous or homozygous p53-knockout mice (p53+/-; p53-/-), as well as knockout mice expressing one allele of p53ser246 (p53+/-, p53*; p53-/-, p53*), do not undergo normal polyploidization with aging and show an increase in the number of cycling (G1-, S-, and M-phase) cells. In addition, p53ser246-transgenic mice (p53+/+, p53*; p53+/-, p53*; and p53-/-, p53*) have a greatly increased number of hepatocytes in the G1 phase. No differences in rates of apoptotic hepatocytes are found among any of the mouse groups studied, so the increased proliferation results in a hyperplasia manifested by a increased number of small periportal cells. We conclude that loss of p53 removes blocks in the cel...Continue Reading

References

Jan 1, 1992·Genes, Chromosomes & Cancer·C Caron de Fromentel, T Soussi
Jul 5, 1991·Science·M HollsteinC C Harris
Jun 6, 1991·Nature·A J LevineC A Finlay
Apr 2, 1987·Nature·R BravoH Macdonald-Bravo
Mar 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·J M AlmendralR Bravo
Oct 1, 1986·Mechanisms of Ageing and Development·K Ohtsubo, T A Nomaguchi
Dec 1, 1973·Experimental Cell Research·J Chemnitz, P Bichel
Jun 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·L YavorkovskyS Sell
Jun 1, 1995·Cancer Metastasis Reviews·J M Lee, A Bernstein
Oct 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·L DumencoN Fausto
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·M NakanishiJ R Smith
May 15, 1995·Genes & Development·C J Sherr, J M Roberts
Mar 3, 1995·Science·S M CrossB J Reid
Dec 16, 1994·Science·L H Hartwell, M B Kastan
Jan 1, 1993·Virchows Archiv. B, Cell Pathology Including Molecular Pathology·B N KudryavtsevG I Stein
Sep 2, 1993·Nature·A DuttaE Winchester
Jan 1, 1993·Molecular and Cellular Biology·J J RyanM F Clarke
Aug 1, 1996·Current Biology : CB·M Winey
Jun 1, 1997·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C O BellamyD J Harrison
Aug 15, 1987·Applied Optics·J W Bacus, L J Grace

❮ Previous
Next ❯

Citations

Apr 16, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·N Ghebranious, S Sell
Jul 26, 2005·Mutation Research·Laura D Attardi, Lawrence A Donehower
Mar 26, 2005·Mutation Research·Undi HofflerBurhan I Ghanayem
Feb 21, 2003·Biochemical and Biophysical Research Communications·Elizabeth A ConnerSnorri S Thorgeirsson
Apr 20, 2001·Toxicology Letters·N C MartinD J Harrison
May 7, 2002·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·M F DonatoM Colombo
Jan 10, 2003·Journal of Gastroenterology and Hepatology·Ritu LakhtakiaSubrat Kumar Panda
Aug 13, 1998·Journal of the National Cancer Institute·K S IwamotoT Seyama
Oct 7, 2006·Current Opinion in Gastroenterology·R H Moseley
Dec 28, 2002·Molecular Carcinogenesis·Chuanwei YangStewart Sell
Aug 11, 2000·Seminars in Cancer Biology·S Gupta
Mar 11, 2003·The Journal of Biological Chemistry·Jacques-Emmanuel GuidottiChantal Desdouets
Jan 31, 2002·World Journal of Gastroenterology : WJG·Xiao-Mou PengZhi-Liang Gao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.

Adrenocortical Carcinoma

Hepatocellular carcinoma is the most common type of primary liver cancer and frequently occurs in individuals with chronic liver diseases like cirrhosis. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis